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Optic nerve hypoplasia iPSC derived retinal ganglion cells exhibit differential gene expression with potential relevance to disease etiology

ABSTRACT: Optic nerve hypoplasia iPSC derived retinal ganglion cells exhibit differential gene expression with potential relevance to disease etiology

PROVIDER: PRJNA947606 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23940507.fastq.gz	Fastqsanger.gz
	SRR23940508.fastq.gz	Fastqsanger.gz
	SRR23940509.fastq.gz	Fastqsanger.gz
	SRR23940510.fastq.gz	Fastqsanger.gz
	SRR23940511.fastq.gz	Fastqsanger.gz

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Optic nerve hypoplasia iPSC derived retinal ganglion cells exhibit differential gene expression with potential relevance to disease etiology

Project description:To investigate gentic contributions to optic nerve hypoplasia, induced pluripotent stem cells were produced from 3 patients and 3 controls. The iPSCs were differentiated to retinal organoids from which differential gene expression was performed on FACS isolated retinal ganglion cells.

2023-05-01 | GSE227975 | GEO

Transcriptional profiling of adult retinal ganglion cells during optic nerve regeneration

Project description:Objective: To identify genes that are differentially expressed in retinal ganglion cells undergoing axon regeneration after optic nerve injury. Adult mice that express cyan-fluorescent protein (CFP) in RGCs were treated with pro-regenerative treatment after optic nerve injury. The treated RGCs were selected by FACS (CFP+mcherry) and their RNA profiles were analyzed.

2020-12-29 | GSE142881 | GEO

Transcriptional profiles of mouse retinal ganglion cells after optic nerve crush [RGC_injury_2019-9205_He]

Project description:The removal of the Structure Specific Recognition Protein 1 (Ssrp1) gene from retinal ganglion cells has been shown to improve their survival after acute optic nerve injury in mice. To investigate the transcriptional mechanisms underlying the negative regulation of neuronal survival by Ssrp1, we obtained the bulk transcriptome of pooled RGCs at several time points (1, 2, 3, and 4 days) after optic nerve injury.

2025-05-16 | GSE233822 | GEO

Expression data from mouse optic nerve head after optic nerve crush

Project description:Reactive gliosis is a complex process that involves profound changes in gene expression. We used microarray to indentify differentially expressed genes and to investigate the molecular mechanisms of reactive gliosis in optic nerve head in response to optic nerve crush injury. C57Bl/6 female mice were 6-8 weeks old at the time of optic nerve crush surgery. The optic nerve in the left eye was crush 1 mm behind the globe for 10 seconds and the right eye served as contralateral control. The animals were allowed to recover for 1 day, 3 day, 1 week, 3 weeks and 3 months before the optic nerve heads were collected. The naive control mice did not receive any surgery in either eye. Due to the small tissue size of the mouse optic nerve head, two optic nerve heads were pooled together for each microarray chip. The left eyes and the right eyes of two mice were combined respectively to form one pair of experiment and control samples. There were five biological replicates (10 mice) for each condition.

2013-07-15 | E-GEOD-40857 | biostudies-arrayexpress

Molecular Characterization of Pontocerebellar Hypoplasia

Project description:Molecular Characterization of Pontocerebellar Hypoplasia

| PRJNA1062911 | ENA

Molecular Characterization of Pontocerebellar Hypoplasia

Project description:Molecular Characterization of Pontocerebellar Hypoplasia

| PRJNA1062912 | ENA

Astrocytes of the optic nerve exhibit a region-specific and temporally distinct response to elevated intraocular pressure

Project description:The optic nerve is an important tissue in glaucoma and the unmyelinated nerve head region remains an important site of many early neurodegenerative changes. In humans and mice, astrocytes constitute the major glial cell type in the region, and in glaucoma they become reactive, influencing the optic nerve head (ONH) microenvironment and disease outcome. To determine the response of ONH astrocytes in glaucoma, we studied their transcriptional response to an elevation in intraocular pressure (IOP) induced by the microbead occlusion model. We also assessed the response of astrocytes in the more distal myelinated optic nerve proper (ONP). In this experimental model, astrocytes of the optic nerve exhibited a region-specific and temporally distinct response: ONH astrocytes showed very few early transcriptional changes and ONP astrocytes demonstrated substantially larger changes over the course of the experiment.

2023-10-01 | GSE237073 | GEO

Amacrine cells suppress retinal ganglion cells survival and optic nerve regeneration bu releasing intersynaptic zinc

Project description:Retinal ganglion cells (RGCs) convey the major output of information collected from the eye to the brain. RGCs are irreversibly lost when injured in degenerative diseases such as glaucoma; this failure can be partially reversed by eliminating the retinal mobile zinc (Zn2+) and leads to substantial axon regeneration. ZnT3 conditional knockout in retinal amacrine cells blocks the synaptic transport of Zn2+, which promotes RGC survival and axonal regeneration in optic nerve jinjury (ONC). Here, we conducted an mRNA sequencing of flow cytometry-isolated RGCs 3 days after optic nerve injury with or without ZnT3 expression in retinal amacrine cells.

2023-07-01 | GSE213937 | GEO

Aberrant gene expression yet undiminished retinal ganglion cell genesis in iPSC-derived models of optic nerve hypoplasia.

Project description:BackgroundOptic nerve hypoplasia (ONH), the leading congenital cause of permanent blindness, is characterized by a retinal ganglion cell (RGC) deficit at birth. Multifactorial developmental events are hypothesized to underlie ONH and its frequently associated neurologic and endocrine abnormalities; however, environmental influences are unclear and genetic underpinnings are unexplored. This work investigates the genetic contribution to ONH RGC production and gene expression using patient induced pluripotent stem cell (iPSC)-derived retinal organoids (ROs).Materials and methodsiPSCs produced from ONH patients and controls were differentiated to ROs. RGC genesis was assessed using immunofluorescence and flow cytometry. Flow-sorted BRN3+ cells were collected for RNA extraction for RNA-Sequencing. Differential gene expression was assessed using DESeq2 and edgeR. PANTHER was employed to identify statistically over-represented ontologies among the differentially expressed genes (DEGs). DEGs of high interest to ONH were distinguished by assessing function, mutational constraint, and prior identification in ONH, autism and neurodevelopmental disorder (NDD) studies.ResultsRGC genesis and survival were similar in ONH and control ROs. Differential expression of 70 genes was identified in both DESeq2 and edgeR analyses, representing a ~ 4-fold higher percentage of DEGs than in randomized study participants. DEGs showed trends towards over-representation of validated NDD genes and ONH exome variant genes. Among the DEGs, RAPGEF4 and DMD had the greatest number of disease-relevant features.ConclusionsONH genetic background was not associated with impaired RGC genesis but was associated with DEGs exhibiting disease contribution potential. This constitutes some of the first evidence of a genetic contribution to ONH.

| S-EPMC10841193 | biostudies-literature

Translational profiling of retinal ganglion cell optic nerve regeneration in Xenopus laevis

Project description:Unlike adult mammals, adult frogs regrow and regenerate their optic nerve following a crush injury. Using Translational Ribosome Affinity Purification (TRAP), a method to isolate mRNAs actively undergoing translation in a target cell population, we have generated a transcriptional profile by RNA-Seq for retinal ganglion cells (RGC) during the period of recovery following an optic nerve injury. Based on bioinformatics analysis using the JGI 9.1 Xenopus laevis gene models, our results reveal a profound shift in the composition of actively translating mRNAs during the early stages of RGC regeneration: as factors involved in cell signaling are rapidly downregulated, and those involved in core metabolism are upregulated. We identified one highly upregulated gene in response to injury, uchl1, which coupled to downregulation of the synucleins (snca, scng), was previously implicated in neurodegenerative diseases. Our injury-screen in Xenopus identified a previously unknown gene, gng8, as being associated with the regenerative process. Our generated online database provides the Xenopus community a valuable resource for the identification of genes involved in the regeneration process to target for future functional studies.

2016-11-01 | GSE77724 | GEO

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